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Discordance of DNA methylation variance between two accessible human tissues.

Author(s): Jiang R, Jones MJ, Chen E, Neumann SM, Fraser HB, Miller GE, Kobor MS

Publication: Sci Rep, 2015, Vol. 5, Page 8257

PubMed ID: 25660083 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   This study compared DNA methylation profiles between matched buccal cell specimens and PBMCs. The association between DNA methylation and patient age, gender, ethnicity, and BMI was also investigated. Buccal cell and blood specimens were collected using unspecified methods from 25 healthy volunteers (26 to 45 years old, 15 males and 10 females, 18 Caucasians and 7 non-Caucasians, BMI of 18.18–47.95). PBMCs were isolated from blood using density gradient centrifugation.  Genomic DNA was extracted from PBMCs and buccal cells by an undescribed method, treated with the EZ DNAm kit, and DNA methylation at 1,536 CpG loci and 371 genes was evaluated by microarray.  

   Summary of Findings:

   For each participant, PBMCs had significantly higher mean DNA methylation rates than buccal cells (P=3.16 x 10^-14), but buccal cell specimens had larger overall inter-individual ranges than PBMCs (P=2.05 x 10^-8). Variation between specimen types was higher than individual variation with a correlation coefficient of 0.773 between buccal and PBMC specimens and correlation coefficients among individuals of 0.980 for buccal cells and 0.987 for PBMC. Of the 998 CpG sites analyzed, 537 CpGs (53.8%) were significantly different between PBMCs and buccal cells (P<0.001). This variation between specimen types was mostly due to a higher level of methylation of low CpG density islands sites in PBMC specimens (mean correlation of 0.514) as opposed to high CpG density islands, intermediate CpG density islands, or uncategorized sites (mean correlations of 0.748, 0.757, and 0.795; respectively). Exclusion of sites representative of cellular processes specific to buccal cells or PBMCs resulted in 449 differentially methylated sites. Low CpG density islands which constituted only 21% (212/998) of total CpG sites analyzed, represented 31% of those differentially methylated (P=1.02 x 10^-12). While DNA methylation was not associated with age or ethnicity in either specimen type, both PBMC and buccal cell specimens had methylated CpG sites that were associated with gender but only PBMCs demonstrated a substantial number (>50) that were statistically significant. Similarly, more CpGs were associated with BMI in PBMCs than in buccal cells.

   Biospecimens

   • Cell - Buccal
   • Bodily Fluid - Blood
   • Cell - White Cells

   Preservative Types

   • None (Fresh)

   Diagnoses:

   • Normal

   Platform:

   Analyte	Technology Platform
   DNA	DNA microarray
   DNA	Bisulfite conversion assay

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Patient age	26 to 45 y
   Preaquisition	Patient gender	Female Male
   Preaquisition	Patient race	Caucasian non-Caucasian
   Preaquisition	Patient body mass index	18.18–47.95
   Biospecimen Acquisition	Biospecimen location	Buccal cells Blood
   Biospecimen Acquisition	Method of fluid acquisition	Venipuncture Cheek rubbing during collection

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